MHC class II antigens, HLA-DR in the human and la in the mouse, are membrane-bound glycoproteins encoded by genes of the major histocompatibility complex. Expression of these antigens is of great functional importance for the initiation and perpetuation of immune responses. In a number of immunopathologic conditions, HLA-DR antigen-negative cells are stimulated to express class II antigens. In these cases, an immunologic role has been postulated for the class II antigen expression. We showed that cytokine-activated RPE cells express MHC class II antigens. These la-positive cells can both process retinal antigens and present them to specifically sensitive T-helper lymphoctyes. These studies indicated that cytokine activated RPE cells may be a basic component of ocular immunity. These studies on MHC class II antigen expression in localized autoimmune diseases provide evidence that the activation of these antigens may contribute to the immunopathogenesis of these diseases.